Idiopathic Parkinson's Disease (IPD) is the second most common neurodegenerative disease, affecting an estimated 500,000 Americans; there are 35,000 new cases of IPD annually in the United States. The disease follows a progressive course, culminating in death or severe disability after about 20 years. Although there are medications that help to alleviate the symptoms of IPD by increasing central levels of the neurotransmitter dopamine, there remains no treatment to slow the relentless progression of the underlying degenerative process. A number of potential mechanisms of cell death have been illuminated by studies of pathology, epidemiology and experimental toxin-induced parkinsonism in animals. These include oxidative stress, protein aggregation, mitochondrial dysfunction, indirect excitotoxicity and apoptosis. A number of putative neuroprotective agents including propargylamines, complex I cofactors, substances affecting the mitochondrial energy potential, amantadine and others are emerging from the laboratory or early clinical trials. The Movement Disorders Group, of the Department of Neurological Sciences, Rush Medical College proposes to serve as one of 42 clinical centers for the Parkinson's Disease Neuroprotection Clinical Trial. The Rush Clinical Center will (1) participate in the design and implementation of pilot studies and the large simple clinical trials of 2 or more potential neuroprotective agents (2) recruit up to 12 subjects with early untreated Parkinson's Disease for pilot studies and 2 subjects per month for 36 months in the large simple trial and (3) collaborate with the Coordination and Statistical Centers in timely and accurate data collection and transmission.